On their own, most genetic variations linked to Alzheimer’s disease affect a person’s risk by a minuscule amount. Together, however, they pack a wallop, at least according to a follow-up study led by Rahul Desikan at the University of California, San Francisco, and published January 24 in Brain. In some 600 people without dementia, polygenic hazard scores correlated not only with their extent of amyloid and tau accumulation and cortical shrinkage, but also with their rate of cognitive decline over the following years. Importantly, the paper claims, a person’s polygenic score had predictive power above and beyond that offered by ApoE genotyping or neuroimaging, suggesting it might make a useful screening tool for trials. Curiously, the score also correlated with non-AD pathologies, including cerebrovascular disease and Lewy body inclusions. A commercial polygenic hazard score (PHS) is already being sold to the public.
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